The major theme of this proposed Superfund Hazardous Substances Basic Research Center is the elucidation of mechanisms of exposure and toxicity in humans and Ecosystems to particular Superfund chemicals selected based upon their potential significance with respect to reproductive and developmental effects. The major goals of the Center are as follows: 1) To elucidate mechanisms of reproductive and developmental toxicity of selected chemicals occurring at Superfund sites. Emphasis will be placed on mechanisms pertaining to cellular signaling and receptor interactions involved in vertebrate development. 2) To facilitate the transfer of mechanistic information obtained across particular vertebrate models (mammals and fishes) relevant to human and/or ecological health. 3) To develop highly sensitive and efficient markers for reproductive and developmental toxicities that can be incorporated into human health and ecological assessments. 4) To elucidate chemical mechanisms controlling the transport and fate of selected chemicals in order to improve predictions of human and ecosystem exposures to emissions from Superfund sites. 5) To develop transgenic zebrafish and killifish (Fundulus) models that will contribute to our understanding of reproductive and developmental impacts in vertebrates. This is the central goal of the Research Core. 6) To establish a strategy for elucidating potential exposures in human populations to chemicals emanating from selected Superfund sites in North Carolina and concomitantly communicating this information to health professionals, community leaders, and the public. This is the centrist goal of the Outreach Core. 7) To enhance interdisciplinary research, and graduate and post- graduate training in the biomedical and environmental sciences. The Training Core will build upon existing resources such as, as Duke's Integrated Toxicology Program and will sponsor specific programs (seminars, symposia, courses) Compared specifically to cross-fertilizations among biomedical scientists, environmental scientists and engineers and social scientists.